Serum GLYcomics to Predict Graft Loss and Mortality After Liver Transplantation (GLYGALT)

Validation of Serum GLYcomics to Predict Graft Loss and Mortality After Liver Transplantation

The first 12 months after liver transplantation (LT) are decisive in posttransplant outcome, as almost half of deaths and two thirds of graft loss requiring retransplant occur in the first year after LT. Since delaying retransplantation in those patients that experience an unfavorable posttransplant course directly impacts their outcome, timely decision making is of paramount importance in these individuals. However, balancing the need and right timing for retransplantation in individual patients with a complicated posttransplant course is currently a difficult challenge that relies on imperfect clinical variables and biomarkers, as well as the experienced judgment of the transplant team.

Building on the findings of a pilot study in liver transplant recipients (n = 131) led by the Ghent University Hospital, we want to validate the prognostic performance of the GlycoTransplantTest on a multicentric scale. In this pilot study, a single glycomic signature at day 7 after LT allowed accurate prediction of graft loss at 3 months after LT. The serum glycome of those patients experiencing graft loss was characterized by increased undergalactosylation and an increased presence of fucosylated and triantennary glycans. After statistical modeling, use of an optimized cutoff based on the relative abundance of 13 serum glycans showed a strong association with graft loss at 3 months (odds ratio 70.211; P<0.001; 95% CI: 10.876-453.23).

Using sequential measurements of serum glycomics in liver transplant recipients, we want to prospectively study and validate the predictive value of the serum glycomic signature for graft survival and overall survival at 3-months (primary end point) and 12-months after liver transplantation (secondary end point).

Determination of the serum glycomic profile is a high-throughput technique that allows to study and quantify the relative abundance of sugar chains (glycans) anchored at specific sites of serum proteins. This technique has shown a very strong prognostic value for graft loss at 3-months after liver transplantation in a pilot study at the Ghent University Hospital.

In this large-scale multicentric prognostic study, we will collect serum samples of liver transplant recipients at fixed time points.

Apart from the serum glycomic profile, we will collect data from the patients electronic record: demographic data (gender, age), data directly relevant to the indication of transplant (eg. imaging for primary liver cancer, lab values for diagnosis of end-stage liver disease), and outcome data (graft survival, overall survival, follow-up time). This list is non-exhaustive.

Using this approach, we will demonstrate the predictive validity of serum glycomics in liver transplant recipients for graft survival and overall survival at 3- and 12-months post-LT. Building on these data, the use of a simple blood test could differentiate patients at risk of graft loss and thus represent a paradigm shift directing these patients to timely treatment adaptations.

Study Overview

• Status: Recruiting
• Conditions: Liver Transplant Failure; Prognostic Biomarkers
• Intervention / Treatment: Diagnostic test: GlycoTransplantTest

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Xavier Verhelst, MD, PhD; Phone Number: 0032 9 332 23 71; Email: xavier.verhelst@uzgent.be
• Study Contact Backup: Name: Lorenz Grossar, MD; Phone Number: 0032 494 088 789; Email: lorenz.grossar@uzgent.be

Study Locations

• Belgium
  • Flanders
    • Ghent, Flanders, Belgium, 9000
      • Recruiting
      • Xavier Verhelst
      • Contact: Xavier Verhelst, MD, PhD; Phone Number: +3293322371; Email: xavier.verhelst@uzgent.be
      • Contact: Lorenz Grossar, MD; Phone Number: +32494088789; Email: lorenz.grossar@uzgent.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients active on the waiting list or undergoing a liver transplantation. All indications for liver transplantations are eligible.

Description

Inclusion Criteria:

• Signed and dated patient informed consent document
• Age ≥ 18 years
• Ability to comply with protocol-specified evaluations and scheduled visits
• Diagnosis of end-stage liver disease, primary hepatic malignancy meeting the Milan criteria for liver transplantation, or acute hepatic failure
• Eligible for liver transplantation and/or active on the waiting list for liver transplantation. Individuals eligible and/or active on the waiting list for multiple organ transplantation including the liver (eg. Combined liver and kidney transplantation, or intestinal transplantation) are also eligible for inclusion.
• Consulted the department of Gastroenterology and Hepatology at Ghent University Hospital

Exclusion Criteria:

- Transplantation of one or more organs not including the liver

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No graft loss; Patients receiving liver transplantation that do NOT experience graft loss within 3-months or 12-months after liver transplantation.	Diagnostic test: GlycoTransplantTest; Determination of serum glycomics in the early posttransplant stage, using an optimal cutoff based on statistic modeling.
Graft loss; Patients receiving liver transplantation that experience graft loss within 3-months or 12-months after liver transplantation. Graft loss is defined as either death of the liver transplant recipient (all-cause), or need for retransplantation of the liver.	Diagnostic test: GlycoTransplantTest; Determination of serum glycomics in the early posttransplant stage, using an optimal cutoff based on statistic modeling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft loss	Death or need for retransplantation	3 months after liver transplantation
Mortality	All-cause mortality	3 months after liver transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft loss	Death or need for retransplantation	12 months after liver transplantation
Mortality	All-cause mortality	12 months after liver transplantation

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Universitaire Ziekenhuizen KU Leuven; University Hospital, Antwerp; Cliniques universitaires Saint-Luc- Université Catholique de Louvain; Fund for Scientific Research, Flanders, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Estimated): April 26, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Liver transplantation; Graft survival; Glycomics
• Other Study ID Numbers: ONZ-2023-0061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No